Cancer Antigen 15-3 (CA 15-3) Tumor Marker Testing

CA 15-3 Biomarker Test - Why and When is it Used?

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What is the cancer antigen 15-3 (CA 15-3) blood test for breast cancer, and what does it mean? What are the reasons for ordering a test for this biomarker? What are the normal values of this tumor marker, what are the causes of an increased level, and how often do false positives occur?

Cancer Antigen 15-3 (CA 15-3) - Definition

Cancer antigen 15-3 (CA 15-3) refers to a blood test that may be performed during treatment for breast cancer.

It may be used to look for the recurrence of breast cancer or to monitor the treatment of breast cancer or other conditions.

What is CA 15-3?

CA 15-3 is a protein that is a normal product of your breast tissue. It does not cause breast cancer. If a cancerous tumor (cells growing out of control) is present in your breast, however, your levels of CA 15-3 may increase as the number of cancer cells increase. Tumor cells will shed copies of the CA 15-3 protein, which can be measured by this blood test and by a related test of cancer antigen 27.29 (CA 27.29). Most of the time, either a CA 15-3 test or a CA 27.29 test will be ordered, but not both, as tests used to monitor metastatic breast cancer treatment.

Proteins that can be measured in the blood to monitor the growth of a cancer are referred to as tumor markers or biomarkers—they "mark" the presence of the cancer.

Normal Values of CA 15-3

Lab values may vary depending on the lab, but a normal CA 15-3 level is usually considered to be one that is 30 U/mL or less.

When is a CA 15-3 Biomarker Test Abnormal?

It's important to note that if a CA 15-3 test is elevated, it doesn't necessarily mean you have metastatic breast cancer or even breast cancer at all. Below are mentioned several other conditions which can cause an elevated CA 15-3 level.

On the other hand, a normal CA 15-3 test does not necessarily mean that you are responding to treatment.

Not every breast cancer causes a risk in CA 15-3.

How Common is an Elevated CA 15-3 Tumor Marker with Breast Cancer?

As noted, not every breast tumor causes a rise in CA 15-3, so for patients with tumors that do not produce CA 15-3 or with early-stage breast cancers, this test is not useful. Only about 30 percent of patients with localized breast cancer (cancer limited to the breast) will have increased levels of CA 15-3. In patients with metastatic breast cancer, CA 15-3 can be found in 50 to 90 percent of all cases.

CA 15-3 tumor marker test is most useful in monitoring advanced breast cancer (including the response to treatment) in women who have breast cancer which overproduce CA 15-3. Levels of CA 15-3 tend to be particularly high in women who have liver or bone metastases due to breast cancer.

Sensitivity and Specificity of the CA `5-3 Tumor Marker

If your doctor talks to you about CA 15-3, or if you read about the meaning of this test, you may hear many references to the sensitivity and specificity of the test. Sensitivity refers to the ability to find something. The sensitivity of a test describes how well a test can find something, such as a breast cancer recurrence. If the level of CA 15-3 was always increased when a breast cancer recurred, the sensitivity would be considered 100 percent.

Specificity, in contrast, refers to the ability of a test to specifically find something (such as recurrent breast cancer) instead of something else. If a test has less than 100 percent specificity (as does the CA 15-3) it means that sometimes the test will be positive even if the condition (such as metastatic breast cancer) is not present. When a test such as this is positive, but not due to the condition for which it is ordered, it is referred to as a false positive. Below are listed several conditions other than breast cancer which can result in a positive test, in other words, a "false positive" if the test is indeed ordered to monitor breast cancer.

What a CA 15-3 Does NOT Test For

The CA 15-3 test is not used as a screen for breast cancer, nor is it used as part of the diagnosis of breast cancer.

Reasons to Have a CA 15-3 Tumor Marker Test with Breast Cancer

There are several reasons for which a CA 15-3 test may be helpful. These include:

  • Recurrence - If you have completed treatment for breast cancer your doctor may test your blood for CA 15-3 on a regular schedule to see if your levels of this antigen are rising or remaining steady. Rising levels of CA 15-3 may indicate a recurrence of breast cancer. Since other conditions can cause elevated levels of this antigen, however, the test results must be considered along with the results of imaging studies, your symptoms, and other tests.
  • To monitor treatment - Following levels of CA 15-3 may help your doctor know if your treatment is working. It's important to note, however, that it may take four to six weeks after treatment before a change is seen in the level of CA 15-3. An exception which is important to note is for those women who are treated with the chemotherapy drug Afinitor (everolimus.)​ Due to the way this medication works against breast cancer, the results of a CA 15-3 biomarker test may actually be the opposite of what is happening with your cancer.​
  • To see if your cancer has progressed - If your CA 15-3 level doesn't respond or continues to increase, it may suggest that your cancer is worsening. The level of CA 15-3 is correlated with the degree of spread of a breast cancer and is often particularly high when bone and liver metastases are present. While CA 15-3 is often elevated with the increased spread of metastatic breast cancer, it is not always very good in estimating your prognosis. 
  • To monitor other conditions which may be detected via a CA 15-3 test.

Other Conditions Which May Cause an Elevated CA 15-3

There are several conditions—both cancerous and benign—which can cause an elevation of the CA 15-3 level in your blood. Some of these include:

Coping with an Elevated CA 15-3 Level

If your CA 15-3 tumor marker is elevated, and it's it felt to be related to the spread of breast cancer, you and your doctor will look at several other factors in making decisions about further tests as well as treatment. Some of these include the size of your tumor, other tumor marker tests, the results of imaging studies, as well as any findings from your history or physical exam. It can be frightening looking at a lab test which is abnormal, but there are many other factors that go into determining the next step and your prognosis, beyond lab values.

You may wish to take a look at some of the treatment options for metastatic breast cancer. There are many clinical trials in progress, and newer treatments are becoming available each year. One of the most important things you can do as a breast cancer survivor (or a survivor of any chronic condition) is to be your own advocate in your cancer care. In learning about tumor markers such as CA 15-3, you have taken a very important step into doing just that. Finally, if you are being treated with the cancer drug Afinitor (everolimus), it's important to understand that the results of your CA 15-3 may not be representative of what's really happening with your cancer.

Sources:

Fejzic, H., Mujagic, S., Azabagic, S., and M. Burina. Tumor marker CA 15-3 in breast cancer patients. Acta Medica Academica. 2015. 44(1):39-46.

Nieder, C., Dalhaug, A., Haukland, E., Mannsaker, B., and A. Pawinski. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy. Journal of Clinical Medicine Research. 2017. 9(3):183-187.

Shao, Y., Zianfu, S., Yaning, H., Chaojun, L., and H. Liu. Elevated Levels of Serum Tumor Markers CEA and CA15-3 are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer. PLoS One. 2015. 10(7):e0133830.

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